The emerging role of CDK4/6i in HER2-positive breast cancer

Ciara C. O’Sullivan, Vera J. Suman, Matthew P. Goetz

Research output: Contribution to journalReview article

Abstract

Prior to the advent of the monoclonal antibody trastuzumab, human epidermal growth-factor receptor 2 (HER2)-positive (HER2+) breast cancer (BC) was associated with an aggressive clinical course and poor survival outcomes. In the era of effective HER2-directed therapies, median survival rates for patients with metastatic HER2+ BC now approach 5 years. Despite these improvements, the majority of affected patients unfortunately die from disease. Therapies to overcome treatment resistance are being actively pursued. One strategy has been to target the cyclin-dependent kinases 4/6 (CDK4/6), as they are downstream of HER2 and many of the cellular pathways driving resistance to HER2-targeted therapies, and play a key role in proliferation by controlling transition through the G1 restriction point to the S phase of the cell cycle. In this article, we review the published literature with regard to the rationale for CDK4/6-directed therapies in HER2+ BC and discuss ongoing clinical research and new challenges in the field.

Original languageEnglish (US)
JournalTherapeutic Advances in Medical Oncology
Volume11
DOIs
StatePublished - 2019

Keywords

  • CDK4/6 inhibitor
  • HER2+ breast cancer
  • HER2-targeted therapy
  • breast cancer
  • metastasis

ASJC Scopus subject areas

  • Oncology

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